This invention concerns the preservation of organs for use in transplanting and the like and more particularly concerns apparatus for controlling the redox potential of perfusates used in organ preservation.
A number of methods of organ preservation are available, including inter alia freezing the organ, chilling the organ to a low temperature in a balanced electrolyte bath (hypothermia), storing the organ in an electrolyte bath at normal temperatures with a positive pressure oxygen atmosphere above it (hypobaria), and pumping an oxygenated nutrient medium (a perfusate) through the organ to be preserved (perfusion). Focusing particularly on perfusion, a great deal of work has been done on optimizing various parameters such as temperature, flow rate of the perfusate, perfusate media, and additives to the perfusate. In the course of oxygenating perfusates, the normal oxidation/reduction (redox) potential cannot be maintained without affecting cellular components in the perfusate or in the organ being preserved.
In general, the organ to be preserved is incapable of overcoming the corrosive conditions of its perfusate and as a result develops membrane and mitochondrial damage. For example, hearts removed for preservation are somewhat anoxic. Since biochemical redox reactions are ubiquitous in the cells of the organ and in the reduced state during anoxia, it has generally been thought that extreme alterations in the redox state would not result in pathologic changes in the organ being preserved by perfusion. However, in the extreme anoxic state, hydrogen (which cannot be accepted by pyruvate to form lactate because of system saturation) accumulates, resulting in a redox potential sufficiently low that sulfhydryl linkages are reduced. Breaking the sulfide bridges disrupts the tertiary structure of the proteins, thus modifying or eliminating their function. This event is generally believed to be reversible under ideal conditions. However, rapid reoxygenation of the organ can cause reconnection of the disulfide bridges in incorrect combinations at a time when the cells have no reductive facilities to reverse these mismatches. These incorrect combinations occur soon after the redox potential has shifted from the extreme reduced state to the extreme oxidized state in uncontrolled perfusions. The damage done to the proteins manifests itself in the membrane of each cell, in the sarcoplasmic reticulum, and in the membranes of the mitochondria, thereby causing malfunction of the electron transport system and instability of the lysosomal membrane. It has been suggested, therefore, that the preservation of organs by perfusion could be further improved by maintaining the redox potential of the perfusate at some optimum level. However, apparatus for doing so have suffered from several deficiencies, among them lack of adequate control of the redox potential of the perfusate, insufficient flow rate of the perfusate through the apparatus, complexity of the apparatus, and expense of the apparatus.